Grading and management of CRS from CAR-T
| Grade . | UPenn criteria55,56 . | NCI criteria67 . | Management . |
|---|---|---|---|
| Grade 1 | Mild reaction treated with supportive care, such as antipyretics, antiemetics | Nonlife-threatening symptoms that require symptomatic management | Vigilant supportive management |
| For example, fever, nausea, fatigue, headache, myalgias, malaise | Antipyretics, analgesics | ||
| Monitor fluid balance | |||
| Rule out infections | |||
| Grade 2 | Moderate reaction with signs of organ dysfunction related to CRS, not attributable to other etiologies (eg, grade 2 creatinine or grade 3 LFT elevation) | Symptoms require and respond to moderate intervention | No extensive comorbidities or older age |
| Hospitalization for management of CRS-related symptoms, including fevers with associated neutropenia or need for intravenous therapies (other than intravenous fluids for hypotension) | Oxygen requirement <40% or hypotension responsive to fluids or low dose of one vasopressor | Vigilant supportive management as above; extensive comorbidities or older age | |
| Vigilant supportive care | |||
| Grade 2 organ toxicity | + Tocilizumab | ||
| ± Corticosteroids | |||
| Grade 3 | More severe reaction | Symptoms require and respond to aggressive intervention | Vigilant supportive care as above |
| Hospitalization required for organ dysfunction, including grade 4 LFT elevation or grade 3 creatinine elevation related to CRS and not attributable to any other conditions (excludes management of fever or myalgias but includes hypotension treated with intravenous fluids defined as multiple fluid boluses for blood pressure support or low-dose vasopressors) | Oxygen requirement ≥40% | Vasopressors as needed | |
| Coagulopathy requiring fresh frozen plasma, cryoprecipitate, or fibrinogen concentrate | Hypotension requiring high-dose or multiple vasopressors | + Tocilizumab | |
| Hypoxia requiring supplemental oxygen (nasal cannula oxygen, high-flow oxygen, CPAP, or BiPAP) | Grade 3 organ toxicity or grade 4 elevation in transaminases | ± Corticosteroids | |
| Patients admitted for management of suspected infection due to fevers and/or neutropenia may have grade 2 CRS | |||
| Grade 4 | Life-threatening complications | Life-threatening symptoms | Vigilant supportive care as above |
| Hypotension requiring high-dose vasopressors | Requiring ventilator support | Vasopressors as needed | |
| Hypoxia requiring mechanical ventilation | Grade 4 organ toxicity other than transaminase elevation | +Tocilizumab | |
| ± Corticosteroids | |||
| Grade 5 | Death | Death |
| Grade . | UPenn criteria55,56 . | NCI criteria67 . | Management . |
|---|---|---|---|
| Grade 1 | Mild reaction treated with supportive care, such as antipyretics, antiemetics | Nonlife-threatening symptoms that require symptomatic management | Vigilant supportive management |
| For example, fever, nausea, fatigue, headache, myalgias, malaise | Antipyretics, analgesics | ||
| Monitor fluid balance | |||
| Rule out infections | |||
| Grade 2 | Moderate reaction with signs of organ dysfunction related to CRS, not attributable to other etiologies (eg, grade 2 creatinine or grade 3 LFT elevation) | Symptoms require and respond to moderate intervention | No extensive comorbidities or older age |
| Hospitalization for management of CRS-related symptoms, including fevers with associated neutropenia or need for intravenous therapies (other than intravenous fluids for hypotension) | Oxygen requirement <40% or hypotension responsive to fluids or low dose of one vasopressor | Vigilant supportive management as above; extensive comorbidities or older age | |
| Vigilant supportive care | |||
| Grade 2 organ toxicity | + Tocilizumab | ||
| ± Corticosteroids | |||
| Grade 3 | More severe reaction | Symptoms require and respond to aggressive intervention | Vigilant supportive care as above |
| Hospitalization required for organ dysfunction, including grade 4 LFT elevation or grade 3 creatinine elevation related to CRS and not attributable to any other conditions (excludes management of fever or myalgias but includes hypotension treated with intravenous fluids defined as multiple fluid boluses for blood pressure support or low-dose vasopressors) | Oxygen requirement ≥40% | Vasopressors as needed | |
| Coagulopathy requiring fresh frozen plasma, cryoprecipitate, or fibrinogen concentrate | Hypotension requiring high-dose or multiple vasopressors | + Tocilizumab | |
| Hypoxia requiring supplemental oxygen (nasal cannula oxygen, high-flow oxygen, CPAP, or BiPAP) | Grade 3 organ toxicity or grade 4 elevation in transaminases | ± Corticosteroids | |
| Patients admitted for management of suspected infection due to fevers and/or neutropenia may have grade 2 CRS | |||
| Grade 4 | Life-threatening complications | Life-threatening symptoms | Vigilant supportive care as above |
| Hypotension requiring high-dose vasopressors | Requiring ventilator support | Vasopressors as needed | |
| Hypoxia requiring mechanical ventilation | Grade 4 organ toxicity other than transaminase elevation | +Tocilizumab | |
| ± Corticosteroids | |||
| Grade 5 | Death | Death |
BiPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; LFT, liver function tests.